Trifluoroacetic acid → N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-3-(((tetrahydro-2H-pyran-4-yl)amino)methyl)benzamide

HRID 880270Notes

Reaction equation

[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:38])[CH2:13][NH:14][C:15]([C:17]1[CH:18]=[C:19]([CH:35]=[CH:36][CH:37]=1)[CH2:20][N:21]([CH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1)C(=O)OC(C)(C)C)=[O:16].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:38])[CH2:13][NH:14][C:15](=[O:16])[C:17]1[CH:37]=[CH:36][CH:35]=[C:19]([CH2:20][NH:21][CH:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)[CH:18]=1

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of tert-butyl 3-((3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)carbamoyl)benzyl(tetrahydro-2H-pyran-4-yl)carbamate (450 mg, crude) in DCM (6 mL) was added TFA (6 mL). The mixture was stirred at 25° C. for 16 h. The reaction solution was concentrated, and the residue was purified by prep-HPLC to give the title product (200 mg, 54.9%). 1H NMR (CD3OD, 400 MHz): δ 8.08 (s, 1H), 8.00-7.89 (m, 1H), 7.81-7.68 (m, 1H), 7.58 (s, 1H), 7.39-7.15 (m, 4H), 4.75-4.47 (m, 2H), 4.46-4.39 (m, 1H), 4.34 (s, 2H), 4.05 (dd, J=11.6, 3.6 Hz, 2H), 3.98-3.70 (brs, 1H), 3.62-3.55 (m, 2H), 3.55-3.45 (m, 4H), 3.45-3.32 (m, 2H), 3.32-3.06 (m, 2H), 2.22-2.07 (m, 2H), 1.89-1.72 (m, 2H). LCMS (m/z): 424.2 (M+1).

Workup

concentrationThe reaction solution was concentrated
customthe residue was purified by prep-HPLC

Sources & evidence

ORD record: ord-af8a2d8f0dd249f59f277b19482f99e7
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08993555B2

Reaction notes

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